CTRI Number	CTRI/2022/05/042586 [Registered on: 17/05/2022] Trial Registered Prospectively
Last Modified On:	04/03/2024
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Drug
Study Design	Randomized, Parallel Group Trial
Public Title of Study Modification(s)	Role of Vitamin C supplement as an adjunct to tuberculosis treatment
Scientific Title of Study Modification(s)	Role of Vitamin C supplement as an adjunct to tuberculosis treatment in new smear sputum positive pulmonary tuberculosis – An exploratory trial
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)	Name  Dr C Padmapriyadarsini   Address  No.1.Mayor Sathyamoorthy Road, Chetpet, Chennai Chennai TAMIL NADU 600031 India  Phone  9498022949   Fax     Email  padmapriyadarsinic@nirt.res.in
Details Contact Person Scientific Query	Name  D Bella Devaleenal   Address  No.1.Mayor Sathyamoorthy Road, Chetpet,Chennai Chennai TAMIL NADU 600031 India  Phone  09841746690   Fax     Email  bella.d@nirt.res.in
Details Contact Person Public Query	Name  D Bella Devaleenal   Address  No.1.Mayor Sathyamoorthy Road, Chetpet,Chennai Chennai TAMIL NADU 600031 India  Phone  09841746690   Fax     Email  bella.d@nirt.res.in
Source of Monetary or Material Support	Indian Council of Medical Research
Primary Sponsor	Name  ICMR National Institute for Research in Tuberculosis   Address  No.1, Mayor Sathyamoorthy road ,Chetpet,Chennai, Tamil Nadu, 600031  Type of Sponsor  Research institution
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 3   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr D Bella Devaleenal  ICMR-National Institute for Research in Tuberculosis   Department of Clinical Research, No.1.Mayor Satyamoorthy Road, Chetpet Chennai   09841746690 bella.d@nirt.res.in  Dr Devarajulu Reddy   ICMR-National Institute for Research in Tuberculosis   ICMR-NIRT Vellore Unit, OPD 12A, Govt. Vellore Medical College and Hospital, Adukambarrai, vellore, 632011, Tamil Nadu, India Vellore   09952851859 devarajulu.s@nirt.res.in  Dr S Ramesh Kumar   ICMR-National Institute for Research in Tuberculosis   ICMR-NIRT Department of Clinical Research Madurai unit section, Ward 62, Upstairs, Government Rajaji Hospital, Madurai, TAMIL NADU 625020 India Madurai   09442119695 ramesh@nirt.res.in
Details of Ethics Committee Modification(s)	No of Ethics Committees= 3   Name of Committee  Approval Status  Institutional Ethical and Scientific Committee, Govt Vellore Medical College  Approved  Institutional Ethics Committee, Madurai Medical College and Govt Rajaji Hospital Madurai  Approved  Institutional Ethics Committee, National Institute for Research in Tuberculosis   Approved
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied	Health Type  Condition  Patients  Tuberculosis of lung
Intervention / Comparator Agent	Type  Name  Details  Intervention  Vitamin C 500mg OD  INH Rifampicin Pyrazinamide Ethambutol Vitamin C 500mg OD for 8 weeks followed by INH Rifampicin Ethambutol for 4 months  Comparator Agent  standard of care   INH Rifampicin Pyrazinamide Ethambutol for 8 weeks followed by INH Rifampicin Ethambutol for 4 months   Intervention  Vitamin C 500mg BD  INH Rifampicin Pyrazinamide Ethambutol Vitamin C 500 mg BD for 8 weeks followed by INH Rifampicin Ethambutol for 4 months
Inclusion Criteria	Age From  18.00 Year(s) Age To  60.00 Year(s) Gender  Both  Details  Adult patients aged between 18 – 60 years (both ages inclusive). Patients should have at least two sputum smear samples positive for tubercle bacilli (at least 1+). Newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary tuberculosis (or with less than 7 days of ATT). Sputum sensitive to INH and RIF Willing for study procedures Patients should be residing in or around clinical trial sites geographical location. A chest X-ray picture which in the opinion of the Investigator is compatible with tuberculosis Female participants of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control (i.e. tubal ligation, vaginal diaphragm, intrauterine device, condom or sponge with spermicide, oral contraceptives, contraceptive implant, combined hormonal patch, combined injectable contraceptive or depot-medroxyprogesterone acetate, partner(s) has had a vasectomy) throughout the treatment period in the trial. Patient should express willingness to attend the treatment centre for supervised treatment Patient should express willingness to give written informed consent prior to all trial-related procedures including HIV testing. No history of intolerance, allergy or contraindication to any of the drugs to be administered
ExclusionCriteria	Details  TB Patients with body weight less than 30 kgs Clinically significant evidence of extrapulmonary tuberculosis (miliary tuberculosis, abdominal tuberculosis, urogenital tuberculosis, osteoarthritic tuberculosis, tuberculous meningitis), as judged by the investigator. Uncontrolled Diabetes Mellitus (Hb A1C > 8 %) Patient sero-positive for HIV antibodies, serology tests positive for Hepatitis B surface antigen or Hepatitis C virus antibody Pregnancy or lactating females On treatment with immunosuppressive drugs Glucose 6-phosphate dehydrogenase deficiency Clinical and /social condition deemed unsuitable/ unsafe for participation in study Evidence of clinically significant metabolic, respiratory ( other than TB) gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities/serious illness (other than the indication being studied). Previous history of tuberculosis. Known or suspected alcohol dependence within the past 6 months (audit score of 8 or more) or drug abuse, that is, in the opinion of the investigator, sufficient to compromise the safety or cooperation of the patient. Patients with hepatic or renal disease as evidenced by clinical or biochemical abnormalities i.e., history of liver disease, current ALT > 2.5 times ULN or total bilirubin concentration >1.2 times ULN, Serum Creatinine >1.2 mg/dL, Blood Urea >43 mg/dL Haemoglobin concentration <7.0 g/dL or platelet count <150,000/mm3, or white blood cell count <4500 cells/μL Use of any therapeutic agents known to alter any major organ function (e.g., barbiturates, opiates, phenothiazines, cimetidine) within 30 days prior to dosing.
Method of Generating Random Sequence	Stratified randomization
Method of Concealment	Sequentially numbered, sealed, opaque envelopes
Blinding/Masking	Open Label
Primary Outcome	Outcome  TimePoints  The primary endpoint will be the time from treatment initiation to the first of the two consecutive negative sputum cultures without an intervening positive culture in MGIT culture within the first 8 weeks. (Time to sputum culture conversion is defined as the time interval between the date of treatment initiation and the first date of two consecutive negative cultures taken at least 7 days apart).   8 weeks
Secondary Outcome	Outcome  TimePoints  Drug concentrations and PK parameters of RMP, INH, PZA in adults with newly diagnosed sputum positive drug sensitive pulmonary TB patients in both the treatment arms Median time to detection (TTD) of Mycobacterium tuberculosis in MGIT culture and smear microscopy grade through 8 weeks of therapy between those receiving Vitamin C containing ATT regimen and the standard regimen. The proportion of patients with negative sputum cultures at weeks 1, 2, 3, 4, 5, 6, 7, 8 and at end of treatment   weeks 1, 2, 3, 4, 5, 6, 7, 8 and at end of treatment
Target Sample Size	Total Sample Size="480" Sample Size from India="480"
Phase of Trial	Phase 2
Date of First Enrollment (India) Modification(s)	01/06/2022
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="1" Months="6" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Not Yet Recruiting
Publication Details	nil
Brief Summary	A phase II trial to study the role of Vitamin C as an adjunct to ATT on Sputum culture conversion